INTREPID - IRay Plus Anti-VEGF Treatment For Patients With Wet AMD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for INTREPID - IRay Plus Anti-VEGF Treatment For Patients With Wet AMD (NCT01016873), a randomized phase 2 study. The primary outcome is Number of Lucentis® Injections Up To And Including Week 52.

2. Clinical Question

The main comparison concerns injection use during the first 52 weeks, not a direct measure of visual acuity. All arm descriptions include PRN Lucentis, so the primary endpoint asks whether the average number of those injections differed among the dose and sham groups during the stated period. The registry record also lists visual acuity, time to first PRN injection, and choroidal neovascularization outcomes as secondary measures.

This is a randomized, double-masked, sham-controlled, dose-ranging study. The clinical question is therefore about the posted group-level results for two IRay doses relative to sham in the studied population. It does not, by itself, establish how the findings apply outside that population or address outcomes not reported in the registry record.

3. Trial Design

INTREPID is a phase 2, randomized, parallel-group study with quadruple masking, described in the official title as double-masked and sham controlled. The registry record lists the study status as completed, an enrollment of 230, a start date of 2009-11, and a primary completion date of 2012-05. It describes the objective as confirming safety and establishing effectiveness for two IRay doses in wet AMD.

The arm descriptions pair 16 Gy IRay or 24 Gy IRay with PRN Lucentis, alongside sham IRay with PRN Lucentis. The posted primary outcome is the number of Lucentis injections up to and including Week 52. The arm-level summaries report a mean and standard deviation: 16 Gy IRay, 75 participants, mean 2.64 injections and standard deviation 2.46; 24 Gy IRay, 75 participants, mean 2.44 and standard deviation 2.41; and sham IRay, 80 participants, mean 3.73 and standard deviation 2.58.

The listed secondary outcomes include visual acuity changes and thresholds, time to the first PRN injection, injection counts at several time points, and change in CNV as a percentage of lesion on fluorescein angiography. The record does not report the trial's original statistical analysis plan, its sample-size justification, interim analyses, or the procedures used to define analysis populations. Those omissions limit what can be inferred about planned comparisons and the handling of data after randomization.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

12 Months

24 Months

36 Months

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Lucentis® Injections Up To And Including Week 52, measured over During the first 52 weeks..

The primary endpoint is the number of Lucentis injections up to and including Week 52, described as occurring during the first 52 weeks. It is summarized as a mean with a standard deviation for each arm. The mean describes the average number of injections in the group; the standard deviation describes how spread out individual values are around that average.

Injection count is relevant to the study's stated question because all arms received PRN Lucentis and the trial evaluated whether adding IRay was associated with a different need for those injections. The endpoint therefore captures treatment use over the specified period. It does not directly measure visual acuity, lesion change, or the overall balance of benefits and harms. Those are distinct clinical outcomes, and visual acuity and CNV measures appear among the secondary outcomes.

For the primary comparisons, the posted group means are 2.64 injections for 16 Gy IRay, 2.44 for 24 Gy IRay, and 3.73 for sham IRay. These summaries are descriptive; differences between group means and their uncertainty are needed to interpret the comparisons. The registry record does not report a detailed definition of the analysis population or how missing injection-count data were handled.

7. Results Posted in the Registry

• 16 Gy IRay: mean 2.64 versus 3.73 on control; difference -1.09 (95% CI -1.88 to -0.30), standardized effect d = -0.43; z-test p = 0.007.
• 24 Gy IRay: mean 2.44 versus 3.73 on control; difference -1.29 (95% CI -2.08 to -0.50), standardized effect d = -0.52; z-test p = 0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • 16 Gy IRay: mean -0.16 versus -0.10 on control; difference -0.06 (95% CI -0.20 to 0.08), standardized effect d = -0.21; z-test p = 0.409.
  • 24 Gy IRay: mean -0.18 versus -0.10 on control; difference -0.08 (95% CI -0.22 to 0.06), standardized effect d = -0.28; z-test p = 0.277.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 16 Gy IRay and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 24 Gy IRay and the control. The interval gives the range of effects that remain compatible with the data.

The registry record lists secondary measures covering visual acuity, timing and number of Lucentis injections, and CNV change. The available numerical detail does not support a full assessment of the overall pattern across these outcomes. In particular, the registry record does not report numerical results for every listed secondary measure in the information, so the presence of an outcome in the list should not be mistaken for a reported finding.

The secondary CNV comparison does not provide a clear corroborating pattern for the primary injection-count result: both dose comparisons have confidence intervals that include zero, and their p-values are unadjusted. This outcome measures lesion change rather than injection use, so it addresses a different aspect of the study. It should not be expected to duplicate the primary endpoint or serve as a direct explanation for the injection-count differences.

Secondary outcomes can help describe whether a primary result sits alongside changes in other clinically relevant measures. But interpreting several endpoints together requires attention to multiplicity, outcome definitions, completeness of reporting, and the analysis plan. The registry record does not report a multiplicity strategy or a detailed plan for those analyses. Unadjusted secondary results carry less weight because repeated testing across outcomes can produce apparently notable results by chance, and because the posted numerical detail is incomplete for a broad cross-endpoint comparison.

Accordingly, the secondary results should be treated as contextual rather than as independent confirmation of the primary comparisons. The record does not give enough information to determine whether a particular pattern across visual acuity, injection timing, injection counts, and CNV was prespecified or consistently observed.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Mean Visual Acuity (VA)
• Percentage (Pct.) of Patients (Pts.) Losing < 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
• Percentage (Pct.) of Patients (Pts.) Gaining ≥ 15 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
• Percentage (Pct.) of Patients (Pts.) Gaining ≥ 0 Letters of Best Correct Visual Acuity (BCVA) From Baseline (Base.)
• Time From Mandatory Injection at Day 0 to the First PRN Injection.
• Total Number (No.) of Lucentis® Injections (Inject.) During The First 12, 28, and 104 Weeks.
• Mean Change in Choroidal Neovascularization (CNV) as % of Lesion on Fluorescein Angiography (FA) From Baseline to Week 52

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary endpoint is continuous in the statistical sense used by the registry record: it is a group mean for injection count, accompanied by a standard deviation. Although injection count consists of whole-number events, the mean can be fractional because it averages across participants. The mean gives a compact description of the group; the standard deviation describes variability among observations. Neither summary shows the full shape of the data or how many participants had each particular count.

What does a mean difference represent?

Each comparison is a difference between an IRay arm mean and the sham mean. The reported estimates are -1.09 for 16 Gy IRay versus sham and -1.29 for 24 Gy IRay versus sham. With the subtraction direction used in these comparisons, a negative estimate means the IRay group mean is lower. The estimate describes the size and direction of the observed difference in group averages; it does not describe the experience of every participant.

The standard deviations for the primary endpoint are 2.46, 2.41, and 2.58 for the 16 Gy, 24 Gy, and sham arms, respectively. The comparison calculations use a pooled standard deviation, reported as 2.523 for the 16 Gy comparison and 2.499 for the 24 Gy comparison. Pooling is a way to combine information about spread across the compared groups for an unadjusted comparison. It relies on a model for how group variability is handled; the registry record does not report an investigator analysis using this method.

How should the confidence intervals be read?

A confidence interval expresses uncertainty around an estimated difference under the assumptions of the calculation. It gives a range of values compatible with the data and method, rather than a guarantee that the true difference lies within the particular interval. For the primary comparisons, both reported intervals are below zero. The registry record does not state the confidence level for these intervals, so no level should be assumed when interpreting them.

The interval is important alongside the point estimate. The point estimate gives one value for the contrast, while the interval indicates that the estimate is not perfectly precise. A narrower interval generally indicates greater precision than a wider one, all else being equal. Precision depends on the variability of observations and the amount of information available; an estimate should not be judged by its point value alone.

What do the p-values add?

The primary comparison p-values are unadjusted: 0.007 for 16 Gy IRay versus sham and 0.001 for 24 Gy IRay versus sham. A p-value measures how compatible the observed data are with a specified null model, conditional on the assumptions used for the calculation. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of a difference. Because the record does not report an adjustment for multiple comparisons, the p-values do not account for the number of outcomes or comparisons considered.

The posted comparisons are simple unadjusted recalculations from summary statistics. The registry record reports no analyses for these results. This distinction matters: a recalculation can describe the available group summaries but cannot reproduce unreported choices about covariates, analysis populations, missing observations, or other features of a prespecified analysis. The record does not report those details.

Why might variability matter?

The standard deviation indicates that individual injection counts vary around each group mean. When an outcome is a count, its distribution can have features that a normal approximation does not represent well, such as many observations at particular integer values or a long upper tail. This is a general statistical consideration, not a finding established by the registry summaries. The posted analysis uses mean differences and standard deviations; the individual-level distribution and any assessment of its shape are not reported in the registry record.

Over-dispersion is a general issue for count outcomes: it occurs when the variability is greater than a model's assumed variability. If present and ignored, standard errors and intervals from a model can be poorly calibrated. The posted summary statistics alone do not establish whether over-dispersion was present, and the registry record does not report a count-model analysis. The unadjusted mean comparisons should therefore be read as comparisons of group averages, not as a complete model of the count data.

What can the secondary comparison show?

The secondary CNV outcome is also summarized as a mean and standard deviation, with unadjusted mean differences against sham. Its estimates and intervals describe the group-average change in CNV as a percentage of lesion at Week 52. Those intervals include zero. These calculations are separate from the primary injection-count analysis, and the registry record does not report a multiplicity procedure that would jointly account for primary and secondary outcomes.

In general, examining many outcomes or contrasts increases the chance that some results appear noteworthy by chance. Adjustment methods can control aspects of that multiplicity, but the record does not report which, if any, were planned. The secondary p-values should therefore be interpreted as unadjusted and exploratory rather than as confirmatory evidence independent of the primary analysis.

11. Confidence Intervals and Precision

The primary estimates are -1.09 injections for 16 Gy IRay versus sham and -1.29 for 24 Gy IRay versus sham. Their reported confidence intervals are -1.883 to -0.296 and -2.076 to -0.504, respectively. Both intervals lie below zero, consistent with lower mean injection counts in the IRay arms in these unadjusted comparisons. The intervals also show that the point estimates are not exact measurements; a range of differences remains compatible with the data and calculation method.

The registry record does not state the confidence level, so the intervals should not be assigned a level that is not reported. Their widths also cannot be interpreted as a complete account of uncertainty about the trial: they reflect the recalculation from the posted group summaries, not unreported features such as missing-data handling or adjusted analyses. The p-values, 0.007 and 0.001, are unadjusted and should be read with the same methodological caution.

For the secondary CNV outcome, the reported intervals are -0.203 to 0.083 for 16 Gy IRay and -0.224 to 0.064 for 24 Gy IRay. Each includes zero, so the estimates are compatible with differences on either side of zero under the stated comparison. These intervals are relatively broad in relation to their point estimates, and the group summaries use 29, 28, and 44 participants for the 16 Gy, 24 Gy, and sham arms. The available information therefore supports more cautious interpretation of this secondary comparison than a simple reading of its point estimate alone.

Confidence intervals describe statistical precision under a method; they do not establish clinical importance. The registry record does not report a threshold for a clinically meaningful difference in injection count or CNV. The interval should not be treated as a direct statement about individual outcomes or as a guarantee about results in another population.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations give participants per arm for the two-group comparisons. They are not total events: the event-total convention applies to time-to-event calculations, whereas these are continuous-outcome comparisons. The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect equal to the stated fraction of the observed effect. The trial's own original design assumptions are not reported in the registry record.

The 80% power column gives the modeled number of participants per arm for an 80% chance of detecting the assumed effect under those planning assumptions, if that effect were the true effect. The 90% column uses a higher target chance of detection and therefore generally requires more participants per arm. These are prospective planning quantities, not a way to evaluate whether this completed study had enough power after seeing its results.

Rows planning for 100%, 75%, or 50% of the observed effect consider progressively smaller effects. Smaller effects are harder to distinguish from random variation and need more participants per arm, all else equal. The illustrated figures vary by comparison and assumed effect size. They are planning illustrations based on the observed estimates and variability, not the original trial design calculations. This is not observed power.

For example, planning for 75% of the observed effect in the primary 16 Gy comparison gives 150 participants per arm for 80% power and 201 for 90% power. For the 24 Gy comparison under the same fraction, the corresponding planning figures are 105 and 141 participants per arm. These contrasts illustrate why planning requirements depend on the assumed effect and variability as well as the desired power level.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.090; pooled standard deviation σ = 2.523.
2. n = 2 × (1.96 + 0.842)² × 2.523² / -1.090² = 84.1, rounded up to 85 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.09                      # observed difference in means
sigma <- 2.52267365169202                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1016873)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 85 (80% power), 113 (90% power)
 75% of observed effect: n per arm = 150 (80% power), 201 (90% power)
 50% of observed effect: n per arm = 337 (80% power), 451 (90% power)
power.t.test: 85.1 
Simulated power at n = 85 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple primary comparisons and several secondary outcomes, but does not report a multiplicity plan. The primary injection-count comparisons are unadjusted, as are the secondary CNV comparisons. Without a reported strategy for handling multiple tests, p-values should not be interpreted as if they necessarily controlled the chance of false-positive findings across all outcomes and dose comparisons. The record also does not state which comparisons were intended to be confirmatory.

Missing-data methods are not reported in the registry record. The arm-level denominators are available for the primary outcome, and smaller arm-level denominators are reported for the secondary CNV outcome, but the reasons for those denominators and the handling of unavailable measurements are not stated. It is not possible to infer whether missing observations were excluded, imputed, or handled through another method.

The analysis populations are not reported in the registry record. In particular, the record does not specify which randomized participants were included in each endpoint analysis or whether the analyses followed an intention-to-treat, per-protocol, or other population definition. These details can affect interpretation because estimates may depend on who contributes data to a given outcome.

The record lists no reported analyses for the primary outcome, and no reported analyses for the posted secondary CNV outcome. It also does not report the original statistical analysis plan, interim analyses, or sample-size justification. Those details should not be guessed. The recalculated comparisons are useful descriptions of the posted summaries, but they cannot fill in unreported analysis decisions. Together, these omissions limit the ability to assess how closely the posted results reflect prespecified methods and how robust they are to alternative handling of missingness and multiple testing.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.7%), pulmonary embolism (2.7%), limb operation (2.7%), microcytic anaemia (1.3%), gastrointestinal disorder (1.3%).

The registry record reports serious adverse events among 12 of 75 participants in the 16 Gy IRay arm, 8 of 75 in the 24 Gy IRay arm, and 7 of 80 in the sham arm. Other adverse events were reported among 20 of 75, 23 of 75, and 24 of 80 participants in those respective arms. These are counts of affected participants and the corresponding at-risk group sizes as recorded; they are not adjusted comparisons or estimates of causal effects.

The listed serious-event terms include pneumonia, pulmonary embolism, and limb operation, each reported as 2.7%, as well as microcytic anaemia, gastrointestinal disorder, and rectal haemorrhage, each reported as 1.3%. The registry record does not provide a basis for attributing these events to an intervention or comparing their causes across arms. Deaths are not reported in the registry record.

Safety counts should be interpreted in light of the follow-up and event definitions used by the study. The registry record does not report additional details on those definitions or the timing of events in this information. These figures describe reported adverse events; they do not alone establish the overall safety profile.

16. What the Result Does, and Does Not, Mean

The primary summaries and unadjusted recalculations show lower mean Lucentis injection counts in each IRay arm than in the sham arm during the first 52 weeks. The point estimates and confidence intervals convey the direction and statistical precision of those group-average comparisons. They do not show that every participant had fewer injections, and they do not establish why the group averages differed.

The results are specific to the studied population, the two IRay doses, the sham comparison, the PRN Lucentis regimen, and the stated follow-up period. They do not directly answer questions about visual acuity, longer-term outcomes, or outcomes not numerically reported in the registry record. Although visual acuity and other measures are listed as secondary outcomes, the available results do not establish a consistent overall pattern across them.

Statistical evidence is not the same as clinical importance. The registry record does not report a threshold for a clinically meaningful change in injection count, nor does the primary endpoint alone summarize all potential benefits and harms. The unadjusted p-values also do not account for a reported multiplicity plan, because no such plan is given.

The study's randomized, sham-controlled design is relevant to comparative interpretation, but the registry record lacks information on the original analysis plan, missing-data handling, and analysis populations. The posted recalculations should therefore be understood as comparisons of the available group summaries, not as a full reconstruction of the investigators' analysis. The data describe a result; they do not, on their own, justify a treatment recommendation or a conclusion that an intervention works or does not work.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical endpoint must be interpreted in relation to the question it measures. The primary outcome is injection use, not visual acuity or lesion change. It can describe differences in average use of PRN Lucentis over the specified period, while leaving other clinical dimensions to separate outcomes.

It also shows the value of reporting estimates with uncertainty. Mean differences communicate the observed direction and size of the group contrasts, while confidence intervals show the range of values compatible with the recalculation method. A p-value alone would not convey the same information about magnitude or precision. The group means and standard deviations additionally make clear that the analysis concerns averages amid individual variation.

The study is a useful example of the distinction between an original trial design and a planning illustration based on observed results. The sample-size illustrations vary with the assumed fraction of the observed effect and target power. They can demonstrate how assumptions shape a future planning calculation, but they cannot reveal the investigators' original justification, which is not reported in the registry record.

Finally, the record highlights limits of registry-based interpretation. Unadjusted calculations can provide a transparent reading of posted summaries, but absent details about multiplicity, missing data, analysis populations, and prespecified methods leave important questions unresolved. Statistical interpretation depends not only on the numerical estimate, but also on how the data were selected and analyzed.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary comparison is based on group summaries and simple unadjusted recalculations. The registry record does not provide individual-level data, the distribution of injection counts, an adjusted analysis, or the original statistical analysis plan. Although mean and standard deviation summarize the endpoint, they cannot show whether the count distribution was skewed or concentrated at particular values. The record does not report an assessment of those possibilities.

The primary endpoint covers the first 52 weeks. The registry record lists injection counts at other time points among secondary outcomes, including through Week 104, but the numerical information does not permit conclusions about those time points. The registry record also does not report how missing measurements were handled, why the secondary CNV outcome has different denominators, or which analysis populations were used.

The primary p-values are unadjusted, and no multiplicity procedure is reported. The secondary CNV comparisons also have unadjusted p-values, and their reported intervals include zero. Results from several outcomes should not be treated as independent confirmation without knowing the prespecified testing strategy and the completeness of outcome reporting.

The registry record describes a phase 2 study and reports an enrollment of 230. It does not provide enough information to assess generalizability beyond the enrolled population, or to determine how the study's design assumptions related to the planning illustrations. The serious and other adverse-event counts are descriptive; further event definitions, timing, and attribution details are not reported in this information.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: INTREPID - IRay Plus Anti-VEGF Treatment For Patients With Wet AMD — NCT01016873.
• Registry record last updated 2014-12-05; status last verified 2014-12.
• Results first posted 2014-12-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

INTREPID is a completed phase 2 randomized, parallel, sham-controlled study with quadruple masking, evaluating 16 Gy and 24 Gy IRay alongside PRN Lucentis in wet AMD. The registry record reports enrollment of 230 and identifies the primary endpoint as the number of Lucentis injections through Week 52.

The posted primary summaries show mean injection counts of 2.64 for 16 Gy IRay, 2.44 for 24 Gy IRay, and 3.73 for sham IRay. Unadjusted recalculated comparisons give mean differences of -1.09 and -1.29, respectively, with reported intervals below zero. The secondary CNV comparisons have intervals that include zero. The registry record does not report an original analysis plan, missing-data methods, analysis populations, or multiplicity procedures, so these limitations matter when interpreting the estimates.